In the proposed project, we want to determine whether interferon prevents the incorporation of murine leukemia (MLV), or sarcoma (MSV) virus genome into the cellular genome and identify, on a molecular level, the steps in virus replication which are blocked by interferon treatment. The effect of purified mouse interferon (5 times 10 to the 7th power units/mg protein) on the replication of MLV in acute infection, activation of endogenous virus, and chronic infection has been studied. The results indicate that MLV (AKR-L1 virus) replication in AKR cloned cells is inhibited by interferon treatment in all three systems; however, in contrast to the other examined systems, interferon treatment does not abort MLV infection, but only delays it. Under conditions where interferon treatment significantly inhibits virus, MLV yield does not effect synthesis of the main viral core protein (p30) in the cell. This indicates that the interferon block in this system is not due to general inhibition of protein synthesis. The newly synthesized viral RNA in interferon treated cells will be examined to determine whether, in this system, interferon inhibits pre-or post-transcriptional events in the virus replicative cycle. The effect of interferon on the synthesis of various viral proteins and glycoproteins will be compared to examine whether the observed inhibition in virus production could be explained by selective inhibition on the translational level. The effect of interferon on N and X tropic MLV will also be compared. Finally, the effect of interferon on MSV induced cellular transformation will be examined in a system where the transformation process does not require a helper virus.